The antibacterial defenses of the lung can be quantitated by exposing animals to aerosolized bacteria and determining the rate of decrease of viable bacteria remaining in the lungs with time, a process termed lung bacterial clearance. The net clearance of inhaled bacteria is a complex interaction of several processes, the rates of bacterial multiplication, physical removal from the lungs, phagocytosis by alveolar macrophages, and intracellular killing of bacteria. Marked differences in clearance exist among bacterial species and clearance is frequently depressed in experimentally produced disease states. However, the mechanisms underlying such interspecies differences and the changes in clearance accompanying disease are known. The proposed research will examine these interspecies differences in terms of the stated rate constants, and will further examine the contributions of each of these factors to the altered clearance known to occur with hypoxia and pulmonary edema. In addition, the influence of the route of bacterial exposure, aerosol versus intratracheal instillation, on each of these parameters of clearance will be studied.